title: Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen activator-treated patients.
abstract: BACKGROUND
  Intravenous (IV) Alteplase (tissue plasminogen activator [t-PA]) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients with the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events and functional outcomes.
  
  
  METHODS
  We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the University of California, San Diego, Specialized Programs of Translational Research in Acute Stroke database through January 2013. The imaging positive stroke (IPS) code group comprised patients with neuroimaging evidence of acute ischemic stroke, whereas the imaging negative stroke code (INS) group included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day modified Rankin Scale (mRS) score, and incidence of intracranial hemorrhage; and adjusted for age, admission National Institutes of Health Stroke Scale (NIHSS), prestroke mRS, and diabetes in multivariable models.
  
  
  RESULTS
  We identified 106 patients, 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9 ± 8.2, INS 8.0 ± 5.6, P = .002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, P = .034). The diagnoses in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, prestroke mRS, and diabetes, the INS patients had significantly higher rates (odds ratio 3.04, P = .036) of good functional outcome (90-day mRS score 0-1). Intracerebral hemorrhage (ICH) was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH.
  
  
  CONCLUSIONS
  Because most INS patients were found to have NNCI, which may represent either transient ischemic attack or aborted stroke, and there were no intracerebral hemorrhages in the INS group, our data support the safety of administering IV t-PA to all patients in whom acute ischemic stroke is clinically suspected. We have demonstrated that NNCI patients and stroke mimics are common, and future larger scale prospective studies are required to delineate the true frequencies of each and to evaluate differences in outcomes.
authors.affiliation: Department of Neurosciences, University of California, San Diego, California. Electronic address: ilana.spokoyny@gmail.com.
authors.forename: Ilana
authors.initials: I
authors.lastname: Spokoyny
authors.affiliation: Department of Neurosciences, University of California, San Diego, California; Department of Family and Preventative Medicine, University of California, San Diego, California.
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.affiliation: Department of Neurosciences, University of California, San Diego, California; Department of Family and Preventative Medicine, University of California, San Diego, California.
authors.forename: Karin
authors.initials: K
authors.lastname: Ernstrom
authors.affiliation: Department of Neurosciences, University of California, San Diego, California.
authors.forename: Brett C
authors.initials: BC
authors.lastname: Meyer
authors.affiliation: Department of Neurosciences, University of California, San Diego, California.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hemmen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis* / Q000188:drug therapy*; D002140:California; D003937:Diagnosis, Differential; D003952:Diagnostic Imaging / Q000379:methods; D004185:Disability Evaluation; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000175:diagnosis; D002546:Ischemic Attack, Transient / Q000175:diagnosis* / Q000188:drug therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013997:Time Factors; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Acute stroke diagnosis; acute stroke outcome; imaging; neuroimaging negative cerebral ischemia; stroke mimics; t-PA